Efficacy and safety of tavapadon for Parkinson's disease: a systematic review and meta-analysis of randomized clinical trials

Abstract

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor dysfunction and decline in activities of daily living. Current therapies are limited by long-term complications and adverse effects. Tavapadon, a selective dopamine D1/D5 receptor partial agonist, has emerged as a potential therapeutic alternative. Objective: This systematic review and meta-analysis aims to evaluate the efficacy and safety of tavapadon in patients with PD. Methods: We searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) evaluating tavapadon in patients with PD. The primary outcome was change from baseline in combined MDS-UPDRS Parts II + III. Secondary endpoints included changes in MDS-UPDRS Parts II and III and treatment-related adverse events (TRAEs). Random-effects models were used to estimate pooled mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs). Leave-one-out sensitivity analyses and Baujat plots were performed for all examined outcomes to assess the robustness of the results and identify the source of statistical heterogeneity. Subgroup analyses based on PD stage were also executed. The risk of bias assessment was performed using the RoB2 tool, and certainty of evidence for each outcome was evaluated using the GRADE framework. Results: Four RCTs comprising 1,220 patients were included. Tavapadon significantly improved combined MDS-UPDRS II + III scores (MD = −8.83; 95% CI: −13.55 to −4.12; p = 0.0002; I² = 84.8%), as well as Part III (MD = −5.47; 95% CI: −8.62 to −2.31; p = 0.0007; I² = 65.4%) and Part II scores (MD = −1.53; 95% CI: −2.30 to −0.76; p < 0.0001; I² = 2.6%). Subgroup analyses demonstrated greater benefits in early-stage PD compared to intermediate/advanced disease. However, tavapadon was associated with an increased risk of TRAEs (RR = 1.96; 95% CI: 1.19–3.25; p = 0.0236; I² = 82.5%). All included studies were rated as having a low risk of bias. Certainty of evidence was high for the change in MDS-UPDRS part II endpoint and moderate for the other outcomes due to inconsistency. Conclusion: Tavapadon demonstrated significant improvements in motor symptoms and activities of daily living in patients with PD, particularly reflected by reductions in MDS-UPDRS scores. These findings support the therapeutic potential of selective D1/D5 receptor agonism as an effective strategy to enhance motor function. However, tavapadon was also associated with an increased risk of treatment-related adverse events, highlighting the need to balance efficacy with tolerability in clinical decision-making. Although the direction of benefit was consistent across outcomes, substantial heterogeneity and the limited number of available trials reduce confidence in the precise magnitude of these effects.